A Fatty Acid Oxidation-Dependent Metabolic Shift Regulates Adult Neural Stem Cell Activity

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Marlen Knobloch, Gregor-Alexander Pilz, Bart Ghesquière, Werner J. Kovacs, Thomas Wegleiter, Darcie L. Moore, Martina Hruzova, Nicola Zamboni, Peter Carmeliet, Sebastian Jessberger
Hippocampal neurogenesis is important for certain forms of cognition, and failing neurogenesis has been implicated in neuropsychiatric diseases. The neurogenic capacity of hippocampal neural stem/progenitor cells (NSPCs) depends on a balance between quiescent and proliferative states. Here, we show that the rate of fatty acid oxidation (FAO) regulates the activity of NSPCs. Quiescent NSPCs show high levels of carnitine palmitoyltransferase 1a (Cpt1a)-dependent FAO, which is downregulated in proliferating NSPCs. Pharmacological inhibition and conditional deletion of Cpt1a in vitro and in vivo leads to altered NSPC behavior, showing that Cpt1a-dependent FAO is required for stem cell maintenance and proper neurogenesis. Strikingly, manipulation of malonyl-CoA, the metabolite that regulates levels of FAO, is sufficient to induce exit from quiescence and to enhance NSPC proliferation. Thus, the data presented here identify a shift in FAO metabolism that governs NSPC behavior and suggest an instructive role for fatty acid metabolism in regulating NSPC activity.

Graphical abstract

Teaser

Controlled balance between proliferation and quiescence of neural stem/progenitor cells (NSPCs) is required for lifelong neurogenesis. Knobloch et al. identify a metabolic shift in fatty acid oxidation (FAO) that governs the proliferation of NSPCs. Further, their data suggest an instructive role for FAO in regulating NSPC activity. Thus, Knobloch et al. identify FAO as a key metabolic pathway to regulate NSPC activity.


http://ift.tt/2wgz06N